A singular plasmonic-thermoelectric hollow nanostructure inducing apoptosis and cuproptosis for catalytic cancer therapy

Thermoelectric technology has recently emerged as a distinct therapeutic modality. However, its therapeutic effectiveness is significantly limited by the restricted temperature gradient within living organisms. In this study, we introduce a high-performance plasmonic-thermoelectric catalytic therapy utilizing urchin-like Cu_2-xSe hollow nanospheres (HNSs) with a cascade of plasmonic photothermal and thermoelectric conversion processes. Under irradiation by a 1064 nm laser, the plasmonic absorption of Cu_2-xSe HNSs, featuring rich copper vacancies (V_Cu), leads to a rapid localized temperature gradient due to their exceptionally high photothermal conversion efficiency (67.0%). This temperature gradient activates thermoelectric catalysis, generating toxic reactive oxygen species (ROS) targeted at cancer cells. Density functional theory calculations reveal that this vacancy-enhanced thermoelectric catalytic effect arises from a much more carrier concentration and higher electrical conductivity. Furthermore, the exceptional photothermal performance of Cu_2-xSe HNSs enhances their peroxidase-like and catalase-like activities, resulting in increased ROS production and apoptosis induction in cancer cells. Here we show that the accumulation of copper ions within cancer cells triggers cuproptosis through toxic mitochondrial protein aggregation, creating a synergistic therapeutic effect. Tumor-bearing female BALB/c mice are used to evaluate the high anti-cancer efficiency. This innovative approach represents the promising instance of plasmonic-thermoelectric catalytic therapy, employing dual pathways (membrane potential reduction and thioctylated protein aggregation) of mitochondrial dysfunction, all achieved within a singular nanostructure. These findings hold significant promise for inspiring the development of energy-converting nanomedicines.